Pioglitazone hydrochloride ((.+-.)-5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione monohydrochloride), a thiazolidinedione derivative, is currently under clinical evaluation and is expected to effectively ameliorate the abnormal glucose and lipid metabolism associated with NIDDM or obesity (cf. Y. Momose et al., Chem. Pharm. Bull., 39:1440 (1991)).
T. Sohda, et al., J. Med. Chem. 35:2617-2626 (1992), discloses additional thiazolidinedione derivatives as potent hypoglycemic and hypolipidemic agents. including 5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-2,4-thiazolidinedione , which had the most potent activity, more than 100 times that of pioglitazone.
Another thiazolidine derivative under-going clinical studies as a hypoglycemic agent is englitazone sodium, 5-([3,4-dihydro-2-(phenylmethyl)-2H- 1-benzopyran-6-yl[methyl]-2,4-thiazolidinedione sodium salt) (cf. D. A. Clark et al., J. Med. Chem., 34:319-325 (1991)).
Ciglitazone ((.+-.)-5- [4- [(1-methylcyclohexyl)methoxy]benzyl]-2,4-thiazolidinedione) is characteristic of a new class of thiazolidine antidiabetic agents which lower blood glucose in animal models of noninsulin diabetes mellitus (NIDDM), while actually reducing circulating concentrations of insulin. This is believed to be accomplished by improving the responsiveness of the peripheral tissues to insulin. See, e.g., Chang, et al, Diabetes 32:830-838 (September 1983).
CS-045 is an antidiabetic, thiazolidinedione derivative. Its activity and preparation are described in Drugs Fut. 1991, 16(9).
Also, thiazolidine derivatives useful for the treatment of diabetes are described in U.S. Pat. Nos. 4,287,200; 4,687,777; and 4,572,9 12. Their effect on insulin resistance are described, e.g. in, Chang, et al, Diabetes 32:839-845 (1983) and Chang, et al. Diabetes 32:830-838 (1983).
The preparation of these thiazolidinedione derivatives, especially pioglitazone hydrochloride, includes the reduction of an intermediate previously performed by a troublesome high pressure hydrogenation on a palladium on carbon catalyst. What is needed in the art is an easier, more efficient method for perfoming this reduction.